Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is currently at 170 million people and is predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin according to the blood glucose levels, maintaining near constant glucose levels in the body.
Much of the burden of the disease to the user and to healthcare resources is due to the long-term tissue complications, which affect both the small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and the large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbAlc). [see, DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia by frequent glucose measurements and adjustment of insulin delivery is of utmost importance.
Frequent insulin administration can be done by multiple daily injections (MDI) with syringe or by continuous subcutaneous insulin injection (CSII) with insulin pumps. In recent years, ambulatory portable insulin infusion pumps have emerged as a superior alternative to multiple daily injections of insulin, liberating patients from repeated self-administered injections, and allowing greater flexibility in dose administration.
Insulin pumps can deliver rapid acting insulin 24 hours a day through a catheter placed under the skin. The total daily insulin dose can be divided into basal and bolus doses. Basal insulin can be delivered continuously over 24 hours, and can keep the blood glucose levels in range between meals and overnight. Diurnal basal rates can be pre-programmed or manually changed according to various daily activities.
Insulin boluses can be delivered before meals to counteract carbohydrates loads or during episodes of high blood sugar levels. The amount of insulin in the administered bolus can depend on several parameters:                Amount of carbohydrates (Carb) to be consumed, alternatively defined as “serving”, wherein 1 serving=15 grams of Carbohydrates;        Carbohydrate-to-insulin ratio (CIR), i.e. the amount of carbohydrate balanced by one unit of insulin;        Insulin sensitivity (IS), i.e. the amount of blood glucose value lowered by a unit of insulin;        Current blood glucose levels (CBG; “BG”—blood glucose);        Target blood glucose levels (TBG), i.e. the desired blood glucose levels. TBG for most people suffering from diabetes is in the range of 90-130 mg/dL before a meal, and less than 180 mg/dL 1-2 hours after the start of a meal;        Residual insulin, i.e. the amount of insulin remaining from recent boluses that is still working.        
Several ambulatory insulin infusion devices are currently available on the market. The first generation of portable insulin pump was a “pager like” device attached to a user's belt. The first generation device included a reservoir within the device housing. A long tube delivered insulin from the pump attached to a user's belt to a remote insertion site. Such first generation devices are disclosed in U.S. Pat. Nos. 3,771,694, 4,657,486, and 4,498,843. The first generation devices were uncomfortable, bulky devices with a long tube. Consequently, these first generation devices were rejected by the majority of diabetic insulin users because the devices impacted regular activities, such as sports and swimming. In addition, the long delivery tube excluded some optional remote insertion sites, like the buttocks and the extremities.
To avoid the tubing limitations, another concept, of second generation, was proposed. This next concept included a housing having a bottom surface adapted for contact with the patient's skin, a reservoir disposed within the housing, and an injection needle adapted for communication with the reservoir. These skin adhered devices could be disposed of every 2-3 days like current pump infusion sets. For example, this paradigm was described by Schneider, in U.S. Pat. No. 4,498,843, Burton in U.S. Pat. No. 5,957,895, Connelly, in U.S. Pat. No. 6,589,229, and by Flaherty in U.S. Pat. No. 6,740,059. Other configuration of skin adhered pumps are disclosed in U.S. Pat. Nos. 6,723,072 and 6,485,461. In these patents the pump is composed of one piece and adheres to the patient skin for the entire usage duration. The needle emerges from the bottom surface of the device and is fixed to the device housing. These second-generation skin adhered devices tend to be expensive, bulky and heavy.
The pump/infusion device described in US published Patent Application No. 20070106218 and in the U.S. Provisional Patent Application No. 61/123,509, the contents of which are hereby incorporated by reference in their entireties, is a miniature portable programmable fluid dispenser that has no tubing and can be attached to the patient skin. It is composed of two parts, a disposable part and a reusable part. After connection of the reusable and the disposable parts, the unified device presents a thin profile. The reusable part contains the electronic and driving mechanism, and the disposable part contains reservoir delivery tube and an exit port. In some implementations, the device comprises a remote control unit that can allow data acquisition, programming, and user inputs.
Exercise is a therapeutic tool for people with diabetes. Exercise can increase lifespan and reduce the risk of cardiovascular diseases. However, the physiology of BG regulation during exercise is quite complex, leading to poor glycemic control and/or a decrease in active lifestyle among people with diabetes. BG levels during exercise can depend on a balance between glucose mobilization from the liver and muscle and glucose consumption by the working muscles. For example, when glycogen storage is depleted, fat stores can be accessed for lipolysis.
In the setting of inappropriately high insulin concentration during exercise, hepatic glucose output can be inhibited and unopposed glucose disposal into active muscle can cause hypoglycemia. Hypoglycemia may occur during exercise or be delayed by up to 24-36 hours post-exercise. People with diabetes who suffer from hypoglycemia-associated autonomic failure may be affected from exercise induced hypoglycemia more frequently and more profoundly, creating a vicious cycle of hypoglycemia unawareness.
In the setting of inappropriately low insulin levels or excessive counter-regulatory hormone release (e.g. cortisol, catecholamines), hepatic glucose output can be excessive thus leading to hyperglycemia and potential ketoacidosis. (Canadian Journal of Diabetes 2006; 30(1):72-79).